Imaging PEG-like nanoprobes in tumor, transient ischemia, and inflammatory disease models

Bioconjug Chem. 2015 Jun 17;26(6):1061-9. doi: 10.1021/acs.bioconjchem.5b00213. Epub 2015 May 14.

Abstract

The iron chelator deferoxamine (DFO), approved for the treatment of iron overload, has been examined as a therapeutic in a variety of conditions which iron may exacerbate. To evaluate the potential of DFO-bearing PEG-like nanoprobes (DFO-PNs) as therapeutics, we determined their pharmacokinetics (PK) in normal mice, and imaged their accumulation in a tumor model and in models of transient brain ischemia and inflammation. DFO-PNs consist of a DFO, a Cy5.5, and PEG (5 kDa or 30 kDa) attached to Lys-Cys scaffold. Tumor uptake of a [(89)Zr]:DFO-PN(10) (30 kDa PEG, diameter 10 nm) was imaged by PET, surface fluorescence, and fluorescence microscopy. DFO-PN(10) was internalized by tumor cells (fluorescence microscopy) and by cultured cells (by FACS). [(89)Zr]:DFO-PN(4.3) (5 kDa PEG, diameter 4.3 nm) concentrated at incision generated inflammations but not at sites of transient brain ischemia. DFO-PNs are fluorescent, PK tunable forms of DFO that might be investigated as antitumor or anti-inflammatory agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / pathology
  • Brain Ischemia / diagnosis*
  • Carbocyanines / chemistry
  • Carbocyanines / pharmacokinetics
  • Cell Line, Tumor
  • Deferoxamine / chemistry
  • Deferoxamine / pharmacokinetics*
  • Female
  • Inflammation / diagnosis*
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacokinetics*
  • Male
  • Mice
  • Mice, Nude
  • Nanostructures / analysis
  • Nanostructures / chemistry
  • Neoplasms / diagnosis*
  • Optical Imaging
  • Polyethylene Glycols / pharmacokinetics
  • Positron-Emission Tomography
  • Rats
  • Rats, Wistar

Substances

  • CY5.5 cyanine dye
  • Carbocyanines
  • Iron Chelating Agents
  • Polyethylene Glycols
  • Deferoxamine